System and apparatus comprising a multi-sensor catheter for right heart and pulmonary artery catheterization

ABSTRACT

A system and apparatus comprising a multi-sensor catheter for right heart and pulmonary artery catheterization is disclosed. The multi-sensor catheter comprises multi-lumen catheter tubing into which at least three optical pressure sensors, and their respective optical fibers, are inserted. The three optical pressure sensors are arranged within a distal end portion of the catheter, spaced apart lengthwise within the distal end portion for measuring pressure concurrently at each sensor location. The sensor locations are configured for placement of at least one sensor in each of the right atrium, the right ventricle and the pulmonary artery, for concurrent measurement of pressure at each sensor location. The sensor arrangement may further comprise an optical thermo-dilution sensor, and another lumen is provided for fluid injection for thermo-dilution measurements. The catheter may comprise an inflatable balloon tip and a guidewire lumen, and preferably has an outside diameter of 6 French or less.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Continuation-in-Part of U.S. patent applicationSer. No. 14/874,604, filed Oct. 5, 2015, which is a Continuation of U.S.patent application Ser. No. 14/354,624, filed Apr. 28, 2014, which is anational stage entry of PCT International Application No.PCT/IB2012/055893, entitled “Apparatus, system and methods for measuringa blood pressure gradient”, filed Oct. 26, 2012, which claims priorityfrom U.S. Provisional patent application No. 61/552,778 entitled“Apparatus, system and methods for measuring a blood pressure gradient”,filed Oct. 28, 2011 and from U.S. Provisional patent application No.61/552,787 entitled “Fluid temperature and flow sensor apparatus andsystem for cardiovascular and other medical applications”, filed Oct.28, 2011; all these applications are incorporated herein by reference,in their entirety.

This application is a related to U.S. patent application Ser. No.15/001,347, filed Jan. 20, 2016, entitled “System and ApparatusComprising a Multisensor Guidewire for Use in InterventionalCardiology”, which is a Continuation-in-Part of PCT InternationalApplication No. PCT/IB2015/055240, of the same title, filed Jul. 10,2015, designating the United States, and claiming priority from U.S.Provisional patent application No. 62/023,891, entitled “System AndApparatus Comprising a Multisensor Support Guidewire for Use inTrans-Catheter Heart Valve Therapies”, filed Jul. 13, 2014 and from U.S.Provisional patent application No. 62/039,952, entitled “System AndApparatus Comprising a Multisensor Support Guidewire for Use inTrans-Catheter Heart Valve Therapies”, filed Aug. 21, 2014; all saidapplications are incorporated herein by reference in their entirety.

TECHNICAL FIELD

The present invention relates to a system and apparatus comprising amulti-sensor catheter or a multi-sensor guidewire for use in cardiology,and more particularly to a pulmonary artery catheter for right heartcatheterization and related diagnostic measurements.

BACKGROUND

The above referenced related patent applications disclose multi-sensorguidewires and multi-sensor micro-catheters for use in interventionalcardiology. For example, if a heart valve is found to be malfunctioningbecause it is defective or diseased, minimally invasive methods areknown for repair and replacement of the heart valve, by introduction ofa catheter intravascularly into the heart to access the heart valve.Percutaneous procedures for minimally invasive transcatheter heart valvediagnosis, repair and replacement avoid the need for open heart surgery.These procedures may be referred to as Transcatheter Valve Therapies(TVT).

TVT for valve repair include, for example, procedures such as, balloonvalvuloplasty to widen an aortic valve which is narrowed by stenosis, orinsertion of a mitral clip to reduce regurgitation when a mitral valvefails to close properly. Alternatively, if the valve cannot be repaired,a prosthetic replacement valve may be introduced. Minimally invasiveTranscatheter heart Valve Replacement (TVR) procedures, includingTranscatheter Aortic Valve Implantation (TAVI or TAVR) and TranscatheterMitral Valve Implantation (TMVI), have been developed over the lastdecade and have become more common procedures in recent years.

While there have been many recent advances in systems and apparatus forTVT and for related diagnostic procedures, interventional cardiologistswho perform these procedures have identified the need for improvedapparatus for use in TVT, including apparatus for heart valvereplacement. They are also seeking improved diagnostic equipment thatprovides real-time direct measurements, i.e. within the heart, ofimportant hemodynamic cardiovascular parameters before, during and afterTVT.

The above referenced related U.S. patent application Ser. Nos.14/874,604 and 14/354,624 (now issued to U.S. Pat. No. 9,149,230) havingcommon inventorship and ownership with the present application, disclosea multi-sensor microcatheter and a multi-sensor guidewire. Thesemulti-sensor micro-catheters and guidewires comprise a distal endportion containing multiple optical sensors arranged for measuring bloodpressure at several sensor locations, simultaneously, in real-time.Optionally, they include an optical or electrical sensor for measuringblood flow. The disclosed multi-sensor micro-catheters and multi-sensorguidewires can be configured for use in minimally invasive surgicalprocedures for measurement of intra-vascular pressure gradients, andmore particularly, for direct measurement of a transvalvular pressuregradient within the heart, for any one of the four heart valves.

For example, a transvalvular measurement of pressure across the aorticvalve, i.e. with pressure sensors positioned to measure pressureconcurrently in the ascending aorta and left ventricle, allows forassessment of aortic regurgitation, before and after a TAVI procedure.

A need for improved diagnostic apparatus for right heart catheterization(RHC) and pulmonary artery (PA) catheterization has also beenidentified. For example, RHC may be performed in an Intensive Care Unit(ICU) for monitoring of critically ill patients. In a CardiacCatheterization Lab (Cath Lab), RHC may be used for monitoring anddiagnosis, and in the operating room (OR) for monitoring of importanthemodynamic parameters during cardiac surgery or other high risksurgery.

During RHC and PA catheterization, a special balloon tipped catheter,which may be referred to as a pulmonary artery catheter (PA catheter) ora Swan Ganz (SG) catheter, is introduced through one of the largerveins, e.g. through an internal jugular vein, subclavian vein in theneck, or a median cubital vein in the arm, into the superior vena cava,or through a femoral vein into the inferior vena cava. The catheter tipis then introduced from the vena cava into the right atrium of theheart, advanced through the tricuspid valve into the right ventricle,and then through the pulmonic valve (alternatively called the pulmonaryvalve) into the PA, which is the main artery that carries de-oxygenatedblood from the heart to the lungs. One lumen of the PA catheter extendsfrom the proximal end to an opening at the distal tip. This lumen isfluid filled and is connected at its proximal end to an externallyplaced pressure transducer to enable the pressure at the distal tip tobe monitored. Thus the pressure at the distal tip may be monitored bythe catheter as it is advanced sequentially, firstly into the rightatrium (RA), secondly into the right ventricle (RV) and thirdly into thePA. During these measurements the balloon may be partially inflated toallow the balloon to “float” and be drawn into the PA by the blood flow.Subsequently, after further inflating the balloon, the balloon is drawnby the blood flow and wedges in a smaller pulmonary blood vessel formeasurement of a Pulmonary Capillary Wedge Pressure (PCWP). PCWP is anindirect measure of the left atrial pressure (LAP) and left ventricularend-diastolic pressure (LVEDP). At each point a characteristic pressurewaveform is observed, and pressure measurements are recorded. That is,as the catheter tip is advanced, the observed waveform will changesequentially and show the transition from a RA pressure waveform, a RVpressure waveform, a PA pressure waveform and then a PCWP waveform.

Conventional four lumen/four port PA/SG catheters provide: one lumen forpressure monitoring at the catheter tip using an externally connectedpressure transducer; a balloon inflation lumen; a thermistor lumen; anda fluid injection lumen for measurement of blood flow bythermo-dilution. The port for the pressure transducer may also be usedfor blood sampling, e.g. for measurement of mixed venous oxygensaturation (SvO₂). Some available PA catheters include two pressuresensing lumens, which can be connected to two external pressuretransducers for measurement of pressures in the right atrium and in thepulmonary artery. Advanced PA catheters or SG catheters may also includeseveral additional lumens and ports, e.g. another port for fluidinfusion, and/or one or more ports for cable connections to other typesof monitoring equipment, e.g. for measurement of cardiac output,oximetry, or insertion of a cardiac pacing wire.

By way of example only, the following references provide furtherbackground information and details of insertion techniques,characteristic pressure waveforms, and indications for RHC and PAcatheterization:

-   -   1) Jeremy Fernando, “Pulmonary Artery Catheters”, updated 22        Dec. 2014        (http://lifeinthefastlane.com/ccc/pulmonary-artery-catheters/);    -   2) “Swan-Ganz—right heart catheterization”, NIH National Library        of Medicine, online Medical Encyclopedia, Update Date Aug. 12,        2014        (https://www.nlm.nih.gov/medlineplus/ency/article/003870.htm);    -   3) “Pulmonary artery catheter”, Wikipedia, version last modified        8 May 2016        (https://en.wikipedia.org/wiki/Pulmonary_artery_catheter);    -   4) “Invasive Hemodynamic Monitoring: Physiological Principles        and Clinical Applications” pp. 12-15; Jan M. Headley, RN, BS,        CCRN, Edwards Life Sciences; Irvine, Calif., © 2002        (http://ht.edwards.com/resourcegallery/products/swanganz/pdfs/invasivehdmph        ysprincbook.pdf);    -   5) B. Paunovic et al., “Pulmonary Artery Catheterization”, (c)        2011, updated 3 Jan. 2016        (http://emedicine.medscape.com/article/1824547 (c) 2011);    -   6) “Right Heart Catheterization”, Johns Hopkins Medicine Health        Library, version downloaded August 2016        (http://www.hopkinsmedicine.org/healthlibrary/test_procedures/cardiovascular        /right_heart_catheterization_135,40/);    -   7) “Comparing FFR Tools New wires Pressure Microcatheter”, M.        Kern, Cath Lab Digest, Volume 24, Issue 5, May 2016        (http://www.cathlabdigest.com/article/Comparing-FFR-Tools-New-Wires-Pressure-Microcatheter);

Conventional balloon tipped PA catheters that use a fluid filledcatheter, which is coupled to an externally placed pressure transducer,are relatively inexpensive and durable. However, they measure pressureonly at a single point, i.e. at the tip of the catheter. Thus, thecardiologist must reposition the catheter, i.e. by pushing and pullingthe catheter tip back and forth to position tip to make pressuremeasurements at different locations within the heart. During thisprocedure, there is some risk that repeatedly advancing and pulling-backthe catheter for repositioning tip of the catheter for pressure sensingwill interfere with, or disrupt, normal operation of the heart, e.g.cause cardiac arrhythmias (such as atrial or ventricular fibrillation),interfere with opening and closing of the heart valves, or risk damageto the heart tissues.

Also, pressure sensing catheters have limited accuracy. Measurements maybe affected by technical limitations such as reflection of the pressurewave at the tip and distortion if the catheter is kinked or sharplybent. Inertial artefacts and slow dynamic response (time lag, damping,hysteresis, resonances, frequency filtering) can distort the waveform,in time and amplitude, as it travels through the fluid filled lumen (deVecchi et al., “Catheter induced Errors in Pressure Measurements inVessels: An in-vitro and numerical study” IEEE Transaction on BiomedicalEngineering, Vol. 61, No. 6, June 2014). Measurement errors as much as20 mmHg have been reported (see ref. 2 in Robert G. Grey et al.,“Feasibility of In Vivo Pressure Measurement using a pressure tipcatheter via transventricular puncture”, ASAIO J. 2010 56(3) 194-199.This reference also compares limitations of a Pressure Tipped Catheter(PTC) using a piezo-electric pressure sensor and a conventional fluidfilled pressure sensing catheter.

Limitations of pressure sensing catheters with externally placedtransducers are also discussed in United States patent applicationpublication no. US2011/004198, to Hoch, which discloses a central venouscatheter (CVC) using a piezo-electric pressure sensor. However,electrical pressure sensors of this type have some drawbacks for in vivoapplications, where long thin electrical wires are carrying smallelectrical signals in humid environment, e.g. requirement for electricalisolation of electrical components, significant electrical drift andtemperature sensitivity and electrical interference, such as, cross-talkbetween wires from multiple electrical sensors and from externalelectromagnetic sources within the operating room.

Thus, there is a need for improved or alternative PA catheters fordirect measurements of cardiovascular parameters, including bloodpressure measurements, during RHC and PA catheterization procedures.

An object of the present invention is to provide for improvements oralternatives to known systems and apparatus comprising multi-sensorcatheters or multi-sensor guidewires.

SUMMARY OF INVENTION

The present invention seeks to mitigate one or more disadvantages ofknown systems and apparatus comprising multi-sensor catheters ormulti-sensor guidewires for measuring cardiovascular parameters, and inparticular to provide systems and apparatus with particularapplicability for measurements of hemodynamic parameters during rightheart catheterization (RHC) and PA catheterization.

In one aspect, the present invention seeks to provide a multi-sensorcatheter with particular applicability for measurements of hemodynamicparameters during right heart and pulmonary artery catheterization.

A first aspect of the invention provides a multi-sensor catheter forright heart and pulmonary artery catheterization, comprising:

a length of multi-lumen catheter tubing extending between a proximal endand a distal end, having an outside diameter of ≤8 French, and thedistal end comprising an atraumatic tip;

a plurality of optical sensors and a plurality of optical fibers; asensor end of each optical fiber being attached and optically coupled toan individual one of the plurality of optical sensors;

each optical sensor and its optical fiber being inserted into arespective lumen of the multi-lumen catheter tubing, the sensors beingspaced apart lengthwise to provide a sensor arrangement with saidplurality of optical sensors positioned at respective sensor locationsspaced apart lengthwise within a distal end portion of the cathetertubing;a proximal end of each of the plurality of optical fibers being coupledto an optical input/output connector at the proximal end of the catheterfor connection to an optical control system; andthe plurality of optical sensors of the sensor arrangement comprising atleast three optical pressure sensors at respective sensor locationsspaced apart lengthwise along said length of said distal end portion,with an aperture in the catheter tubing adjacent each optical pressuresensor for fluid contact; andwherein the pressure sensor locations and spacings are configured toplace at least one pressure sensor in each of the right atrium, theright ventricle and the pulmonary artery during right heartcatheterization, for concurrent blood pressure measurements at eachpressure sensor location.

The multi-sensor catheter may further comprise another lumen having aproximal port and an opening at the distal tip of the catheter tubing,said lumen having a diameter which accepts a guidewire, e.g. a standard0.025 inch (0.625 mm) guidewire, to enable the catheter to be insertedover the guidewire. For example, to facilitate insertion into the PA,the guidewire is first steered into the RV and PA, and then the catheteris introduced over the guidewire. The latter facilitates introduction ofthe PA catheter by a more tortuous route, for example when it isintroduced from the inferior vena cava.

The multi-sensor catheter may further comprise an inflatable balloonnear the distal tip, the catheter tubing further comprising a ballooninflation lumen, the inflatable balloon being coupled by the ballooninflation lumen to a balloon inflation port at the proximal end of thecatheter tubing. An inflatable balloon tip allows for introduction ofthe tip of the catheter to be flow directed, i.e. the balloon is floatedand guided by blood flow into the PA, and for measurement of the PApressure waveform and PCWP waveform, similar to a conventional PAcatheter.

When the multi-sensor catheter comprises a balloon tip and a guidewirelumen, a guidewire may be used to facilitate insertion and/or theballoon may be inflated for flow directed insertion. The guidewire lumenis preferably a central lumen. This lumen may also be used for bloodsampling at the tip of the catheter, e.g. for measurement of SvO₂ ormeasurement of cardiac output by the Fick method.

In some embodiments, for direct measurement of blood flow within the PA,the plurality of optical sensors further comprises an optical flowsensor. For example, the flow sensor comprises an opticalthermo-dilution or an optical thermo-convection sensor positionedproximal to the distal tip for placement in the PA and the cathetertubing further comprises a fluid injection lumen having an aperturepositioned for fluid injection into the right atrium and the fluidinjection lumen being coupled at the proximal end of the multi-lumencatheter to a fluid injection port.

The multi-lumen catheter tubing may, for example, have an outsidediameter of between 4 and 7 French and more preferably has an outsidediameter of 6 French (2.000 mm) or less. The optical pressure sensorsare preferably Fabry-Pérot (FP) Micro-Opto-Mechanical System (MOMS)sensors. These optical pressure sensors comprise, for example, standardoptical fibers of 0.155 mm diameter and FP MOMS pressure sensors of0.260 mm diameter at the sensor end of the fiber for sensing pressure.When the catheter has a guidewire lumen which accepts a guidewire, e.g.a standard guidewire of up to 0.025 inch (0.625 mm) diameter, and thesensor arrangement comprises three optical pressure sensors and anoptical flow sensor, and a fluid injection lumen, this four opticalsensor arrangement can be accommodated within a multi-lumen catheterhaving an outside diameter of the multi-lumen tubing of approximately 6French. The guidewire lumen is preferably a central lumen of themulti-lumen catheter, and the other lumens are arranged symmetricallyaround the central lumen. With smaller diameter optical sensors andfibers, and/or for use with a smaller diameter guidewire, smallerdiameter multi-lumen catheter tubing may be used. PA catheters forinsertion through one of the larger veins in the neck or groin aretypically in the range from 4 to 8 French, with 6 or 7 French beingcommonly used. Smaller gauge catheters may be preferred for convenienceor patient comfort, e.g. to allow for insertion through one of the veinsin the upper or lower arm, such as the median cubital vein. Smallerdiameter catheters may be required for pediatric use or neonatal use.

In an embodiment, the proximal end of the multi-lumen catheter comprisesa connection hub, through which each lumen of the multi-lumen catheteris connected to a “tail” comprising an individual length of flexibletubing and respective individual proximal ports. The proximal ports foreach optical sensor comprising said optical input/output connector, andthe optical fibers for each optical sensor extending through from theoptical sensor through its respective individual lumen of themulti-lumen catheter tubing, through the hub and flexible tubing to therespective optical input/output connector for connection to the opticalcontrol system.

Optionally, the catheter comprises radiopaque markers at intervals alongthe length of the catheter to facilitate location of each sensor in use,e.g. by conventional radio-imaging techniques. For example, markers maybe placed at regular intervals along the length, or markers are placednear each sensor. A radiopaque marker may also be placed at the tip ornear the balloon.

The catheter may comprise one or more additional lumens with proximalports, which are provided for fluid injection or fluid infusion, withrespective distal apertures located for injection or infusion of fluidthe right atrium during use. One or more additional lumens andrespective proximal ports may optionally be provided for other purposes,if required.

Embodiments of the present invention provide improved or alternativeguidewire directed catheters and flow directed balloon catheters thatenable direct measurements of cardiovascular parameters, includingmeasurement of pressure concurrently within the RA, RV, and PA, duringRHC and PA catheterization procedures.

Another aspect of the invention provides a multi-sensor catheter forright heart and pulmonary artery catheterization in pediatric orneonatal patients, comprising:

a length of multi-lumen catheter tubing extending between a proximal endand a distal end, having an outside diameter of ≤3 French, and thedistal end comprising an atraumatic tip;

a plurality of optical sensors and a plurality of optical fibers; asensor end of each optical fiber being attached and optically coupled toan individual one of the plurality of optical sensors;

each optical sensor and its optical fiber being inserted into arespective lumen of the multi-lumen catheter tubing, the sensors beingspaced apart lengthwise to provide a sensor arrangement with saidplurality of optical sensors positioned at respective sensor locationsspaced apart lengthwise within a distal end portion of the cathetertubing;a proximal end of each of the plurality of optical fibers being coupledto an optical input/output connector at the proximal end of the catheterfor connection to an optical control system; andthe plurality of optical sensors of the sensor arrangement comprising atleast two optical pressure sensors at respective sensor locations spacedapart lengthwise along said length of said distal end portion, with anaperture in the catheter tubing adjacent each optical pressure sensorfor fluid contact; andwherein the pressure sensor locations and spacings are configured tomeasure concurrent pressure waveforms for at least two locations withinthe heart and pulmonary artery comprising a right atrial pressurewaveform, a right ventricular waveform, a pulmonary artery waveform anda pulmonary capillary wedge position waveform, to provide concurrentblood pressure measurements at each optical pressure sensor location.

A further aspect of the invention comprises a control system formulti-sensor catheters and multi-sensor guidewires, such as, themulti-sensor PA catheters disclosed herein.

The control system comprises a light source and detector, and an opticalinterface for coupling, via respective input/output ports, to each ofthe optical fibers and optical sensors of a multi-sensor catheter ormulti-sensor guidewire; data storage and processing means configured forprocessing optical data indicative of pressure values and optionally,optical or electrical data indicative of flow velocity values; andwherein, for right heart catheterization and pulmonary arterycatheterization, the processing means is further configured forgraphically displaying pressure data comprising a plurality ofconcurrent blood pressure waveforms. Thus, when the multi-sensorcatheter comprises at least three optical pressure sensors, the systemcan process optical data from each sensor and display concurrent bloodpressure waveforms from the right atrium, right ventricle and pulmonaryartery.

The concurrent blood pressure waveforms for each optical sensor may bedisplayed together for comparison, or displayed individually, for one ormore time intervals, and during one or more cardiac cycles. Optionally,graphical flow velocity data may also be displayed concurrently.Advantageously, the processing means is further configured to derive anddisplay hemodynamic parameters from the blood pressure data and flowvelocity data. For example, during right heart and pulmonary arterycatheterization with a multi-sensor catheter as disclosed hereincomprising at least three optical pressure sensors, in addition todisplaying blood pressure waveforms from the right atrium, rightventricle and pulmonary artery, a plurality of numeric values such aspeak pressures, mean pressures, peak-to-peak pressure differentials foreach curve, and pressure differentials or gradients between the rightatrium and right ventricle, and between the right ventricle andpulmonary artery can be displayed in real time.

Correspondingly, in another exemplary embodiment, in use of amulti-sensor guidewire during TAVR, e.g. to assess functioning of theaortic valve, before and after a TAVR procedure, the system may displaynumeric values based on pressure waveforms from the aorta and the leftventricle. For example, in addition to displaying pressure waveformsfrom the aorta and the left ventricle, the system may display aplurality of numeric values such as peak pressures, mean pressures,peak-to-peak pressure differentials for each curve, and pressuredifferentials or gradients between the aorta and the left ventricle. Thesystem may also compute a parameter such as an aortic regurgitationindex (ARi), and display the ARi value in real time.

Accordingly, another aspect of the invention provides a computer programproduct embodied as a non-transitory computer readable medium storinginstructions, for execution in a processor of a control system for amulti-sensor catheter or a multi-sensor guidewire, for processingoptical data received concurrently from a plurality of optical sensorsof the multi-sensor catheter or a multi-sensor guidewire, said opticaldata being indicative of blood pressure, and displaying a correspondingplurality of blood pressure waveforms, and optionally flow velocitydata, and displaying numeric data relating to selected hemodynamicparameters and indexes.

Thus, apparatus and systems comprising a multi-sensor PA catheter areprovided that mitigate one or more problems with known systems andapparatus for RHC and PA catheterization, which allow for diagnosticmeasurements and monitoring of hemodynamic parameters, includingmeasurement of blood pressure concurrently at multiple locations withinthe right heart and PA.

The foregoing and other objects, features, aspects and advantages of thepresent invention will become more apparent from the following detaileddescription, taken in conjunction with the accompanying drawings, ofembodiments of the invention, which description is by way of exampleonly.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, identical or corresponding elements in the differentFigures have the same reference numeral.

FIG. 1 (Prior Art) shows a schematic longitudinal cross-sectional viewof a known type of conventional PA catheter, which may be referred to asa Swan Ganz catheter;

FIG. 2 (Prior Art) shows an enlarged transverse cross-sectional view ofthe PA catheter illustrated in FIG. 1 taken through plane A-A of FIG. 1to show the lumens of the multi-lumen catheter tubing;

FIG. 3 (Prior Art) shows schematic partial cross-sectional view of ahuman heart to illustrate placement of a conventional PA catheter withinthe right heart and the PA for measurement of pressure in the PA and formeasurement of blood flow by thermo-dilution;

FIG. 4 (Prior Art) shows schematic diagrams of a human heart toillustrate schematically placement of the conventional PA catheterwithin the right heart and PA for pressure measurements, at each thefollowing positions: A. in the right atrium (RA); B. in the rightventricle (RV); C. in the pulmonary artery (PA); and D. in a pulmonarycapillary wedge position (PCWP); the underlying plots show examples of asequence of typical blood pressure waveform for each of positions A, B,C and D;

FIG. 5 illustrates schematically a system according to a firstembodiment, comprising an apparatus for right heart and PAcatheterization comprising a multi-sensor PA catheter, which isoptically coupled to a control unit;

FIG. 6 shows a schematic longitudinal cross-sectional view of anapparatus for right heart and PA catheterization comprising amulti-sensor PA catheter according to the first embodiment of thepresent invention;

FIG. 7 shows an enlarged axial cross-sectional view of the multi-lumencatheter illustrated in FIG. 6 taken through plane A-A of FIG. 6;

FIG. 8 shows an enlarged axial cross-sectional view of the multi-lumencatheter illustrated in FIG. 6 taken through plane B-B of FIG. 6;

FIG. 9 shows a schematic partial cross-sectional diagram of a humanheart to illustrate placement of the multi-sensor PA catheter of thefirst embodiment within the right heart and PA for diagnosticmeasurements of hemodynamic parameters, including concurrentmeasurements of blood pressure in the RA, in the RV, in the PA and thePCWP;

FIG. 10 shows a schematic longitudinal cross-sectional view of anapparatus for right heart and PA catheterization comprising amulti-sensor PA catheter according to the second embodiment of thepresent invention;

FIG. 11 shows an enlarged axial cross-sectional view of the multi-lumencatheter illustrated in FIG. 10 taken through plane A-A of FIG. 10; and

FIG. 12 shows an enlarged axial cross-sectional view of the multi-lumencatheter illustrated in FIG. 10 taken through plane B-B of FIG. 10.

FIG. 13A illustrates schematically a graphical display of the controlsystem showing three concurrent blood pressure waveforms from: A. sensorposition P1 in the pulmonary artery (balloon deflated); B. sensorposition P2 in the right ventricle; and C. sensor position P3 in theright atrium; together with selected numeric data comprising hemodynamicparameters derived from the pressure waveforms;

FIG. 13B illustrates schematically a graphical display of the controlsystem showing three concurrent blood pressure waveforms from: D. sensorposition P1 in the pulmonary capillary wedge position with the ballooninflated; B. sensor position P2 in the right ventricle; and C. sensorposition P3 in the right atrium; together with selected numeric datacomprising hemodynamic parameters derived from the pressure waveforms;and

FIG. 14 illustrates schematically a graphical display of the controlsystem showing concurrent pressure waveforms from: A. sensor position P1in the aorta and B. sensor position P2 in the right ventricle, withnumeric data comprising hemodynamic parameters derived from the pressurewaveforms, including an aortic regurgitation index (AR Index).

DETAILED DESCRIPTION OF EMBODIMENTS

As illustrated schematically in the longitudinal cross-sectional viewshown in FIG. 1, a conventional PA catheter 1000, which may be referredto as a Swan Ganz catheter, comprises a length of multi-lumen cathetertubing 1002 having at its distal end 1120 an inflatable balloon 1160.The catheter typically comprises a multi-lumen catheter tubing 1002,such as illustrated in FIG. 2, which is a cross-sectional view throughplane A-A of FIG. 1. By way of example, the catheter tubing shown inFIG. 2 has four lumens 1004-1, 1004-2, 1004-3 and 1004-4, and an outsidediameter of 5 French. Referring back to FIG. 1, there is a hub 1006 atthe proximal end of the catheter with individual proximal ports 1010-1,1010-2, 1010-3, and 1010-4. Ports 1010-1, 1010-2, 1010-3 are coupled byindividual lengths of flexible tubing 1007 through the hub 1006 torespective lumens 1004-1, 1004-2 and 1004-3 of the catheter tubing 1002.Port 1010-4 is an electrical connector for a thermistor 20 which islocated within the fourth lumen 1004-4 proximal to the balloon tip 1160,towards the distal end. Electrical connections for the thermistor 20extend through lumen 1004-4 from the thermistor 20 to an electricalcable 1009 extending from the hub 1006. For simplicity of illustrationof the longitudinal cross-sectional view shown in FIG. 1, the innerwalls of the lumens are not shown.

Traditionally, the multi-lumen catheter tubing 1002 of a Swan Ganzcatheter is colored yellow and each of the ports 1010-1 to 1010-4 iscolor coded. A first lumen 1004-1 provides for inflating the balloon andhas a corresponding proximal port 1010-1 for coupling to an air filledsyringe for inflating and deflating the balloon. The balloon inflationport is conventionally colored red. The balloon 1160 typically has avolume of 0.5 ml to 1.5 ml and is connected to the balloon inflationlumen 1004-1. A second lumen 1004-2 is has an aperture 1012-2 opening atthe distal tip 1120 and is connected at the proximal end to a proximalport 1010-2 (conventionally colored yellow) for connection to anexternally placed pressure transducer, so that, when this lumen isfilled with fluid, the blood pressure at the tip 1120 can be sensed.This port and lumen may also be used for sampling of blood at the tip ofthe catheter. For measurement of flow by thermo-dilution using thethermistor 20, there is third lumen 1004-3, which has a proximalinjectate port (conventionally coloured blue) to allow for injection ofa bolus of cold thermo-dilution fluid; this lumen has an injectateopening 1012-3 a distance of approximately 30 cm from the distal tip1120. The fourth lumen 1004-4 accommodates the thermistor 20, i.e. anelectrical temperature sensor, which is typically located at a distanceof about 4 cm from the distal tip 1120; the electrical wires (not shownin FIG. 1) for the thermistor 20 extend through lumen 1004-4 to aproximal port 1010-4 (conventionally colored yellow) which comprises anelectrical connector for the thermistor T. In this example, the secondlumen 1004-2, which has an opening 1012-2 at the distal tip 1120 andrespective proximal port 1010-2 has a larger diameter to allow forinsertion of a guidewire, e.g. a standard 0.025 inch or 0.018 inchguidewire, to assist with introduction of the PA catheter into the rightheart.

FIG. 3 illustrates schematically a partial cross-sectional view of ahuman heart 500 with a PA catheter 1001 positioned within the rightheart and left branch of the PA. The PA catheter 1001 is similar to thatshown in FIGS. 1 and 2 comprising four lumens, i.e. one for ballooninflation, one for pressure sensing, one for the thermistor and one forfluid injection for measurement of flow by thermo-dilution. Similar tothe catheter shown in FIG. 1, the four lumens are connected through ahub 1006 to proximal ports 1010-1, 1010-2, 1010-3 and 1010-4. The firstlumen 1004-1 opens to the inflatable balloon 1160 and the first lumen isconnected to the balloon inflation/deflation port 1010-1 for connectionto an air filled syringe; the second lumen has an opening 1012-2 at thedistal tip 1120 and a distal port 1010-2. The distal port 1010-2 that isused for the guidewire insertion can also be used either for connectionto an external pressure transducer for measurement of blood pressure atthe distal tip 1120, or, for blood sampling, such as for measuring mixedvenous oxygen saturation (Sv0₂). The third port 1010-3 is the proximalinjection port which is connected to the third lumen 1004-3 (FIG. 2) forfluid injection into the right atrium 521 through opening 1012-3. Thefourth port 1010-4 comprises an electrical connector for the thermistor20 which is located in the fourth lumen 1004-4 near the distal tip 1120.

To position the PA catheter 1001 as illustrated schematically in FIG. 3,the catheter tip 1120 is introduced into the right atrium (RA) 521, e.g.in this example upwards through the inferior vena cava 520, and throughthe atrioventricular (tricuspid) valve 522 and into the right ventricle(RV) 523. During introduction, partial inflation of the balloon 1160allows for blood flow directed insertion. That is, with partialinflation of the balloon 1160 in the right ventricle 523, the tip 1120of the catheter tends to be drawn by the blood flow through the pulmonicvalve 524 into the PA 525 and then from the PA towards the right or leftbranches 526L and 526R of the PA, and towards smaller pulmonary vesselswhich lead to the lungs. Pressure sensing at the tip is achieved by thefluid filled lumen 1004-2 which has opening 1012-2 at the distal tip1120, and a proximal port 1010-2 which is connected to the externallyplaced pressure transducer for monitoring pressure at the catheter tip1120. The port 1010-4 provides for electrical connections for thethermistor 20 (T), which located about 4 cm proximally from the balloontip 1160, for measurement of blood flow by thermo-dilution. Asillustrated schematically in FIG. 3, the opening 1012-3 of the fluidinjection lumen is positioned to allow for injection of a bolus of coldfluid into the right atrium of the heart, for detection of a temperaturechange by the thermistor 20 (T) when the cold fluid reaches the PA 525and its left and right branches 526L and 526R, to measure blood flow bya conventional thermo-dilution technique.

In use of the PA catheter 1001, as illustrated in FIG. 4 (Prior Art),when the tip 1120 of the catheter 1001 is first introduced into theheart 500, e.g., through the superior vena cava as illustrated, and intothe RA 521 (position A), a pressure measurement is made in the RA toassess the RA waveform. Then the tip of the catheter is advanced throughthe tricuspid valve 522 into the RV 523 (position B), and a pressuremeasurement is made within the RV to assess the RV waveform. The balloonis partially inflated so that the blood flow draws the balloon from theright ventricle 523, through the pulmonic valve 524 into the PA 525.When the tip of the catheter is in the PA (position C), the balloon isdeflated, and another pressure measurement is made to assess the PAwaveform. The tip of the catheter is then allowed to be drawn furtherinto the PA and the balloon at the tip of the catheter is furtherinflated. When the inflated balloon wedges in a smaller branch 527 ofthe pulmonary vessels (position D) another pressure measurement is made,called the PA occlusion pressure, or pulmonary capillary “wedge”pressure (PCWP) waveform. PCWP provides an indirect measure of the leftatrial pressure (LAP) and left ventricular end-diastolic pressure(LVEDP). As illustrated by the blood pressure waveform in the low partof FIG. 4, as the catheter tip is advanced, the observed waveformchanges sequentially and show the transition from a RA pressurewaveform, a RV pressure waveform, a PA pressure waveform and then a PCWPwaveform. The cardiac output (CO), which is the amount of blood that theheart pumps per minute, may also be determined during a right-heart andPA catheterization. Pressure measurements may be made before and afteradministration of intravenous (IV) heart medications. The catheter mayneed to be repositioned several times to allow for several pressuremeasurements to be made at each of the different locations A, B, C and Dwithin the heart and PA.

Limitations of conventional PA catheters of this type include:

-   -   Pressure measurements are made by a fluid filled pressure        sensing catheter    -   Pressure is transmitted through fluid filled lumen to a remote        pressure transducer; pressure measurements are not always        accurate.    -   Pressure is measured at the distal tip only, so pressure can be        measured only at one point or location at a time.    -   Pressure measurements are sensitive to relative positioning and        re-positioning of the catheter and pressure transducer, e.g.        raising or lowering it relative to the heart in order to set the        zero pressure (0 cm H₂O) on the transducer.    -   Kinking or bending of the catheter may dampen the characteristic        waveforms seen at each position;    -   There is time lag (and hysteresis) between pressure being        applied to the opening at the tip of the pressure sensing lumen        and transmission of pressure through the fluid filled lumen to        the remote transducer.    -   Pullback and repositioning of the catheter for multiple        measurements may cause cardiac arrhythmias.

A system and apparatus comprising a multi-sensor catheter for use incardiology, which may include diagnostic measurements of cardiovascularparameters during right heart and PA catheterization, according to anembodiment of the present invention will be illustrated and described,by way of example, with reference to a system 2000 comprising amulti-sensor PA catheter 2001, illustrated schematically in FIGS. 5 to9.

Firstly, referring to FIG. 5, this schematic diagram represents thesystem 2000 comprising an apparatus 2001 comprising a multi-sensorcatheter for right heart and PA catheterization procedures, coupled to acontrol system 2150, which comprises a control unit 2151 and userinterface, such as the illustrated touch screen display 2152. Themulti-sensor catheter 2001 comprises some components of a conventionalPA catheter, including multi-lumen catheter tubing 2002. In themulti-sensor catheter of this embodiment, the catheter tubing comprisesseven lumens 2004-1 to 2004-7, as illustrated in the transversecross-sectional view in FIG. 7, which is a cross-section through A-A ofFIGS. 5, 6 and 9. Typically, the catheter tubing 2002 has an outsidediameter in the range of about 3-8 French (see Table 1 below forequivalent dimensions in mm and inches), and extends to an atraumaticflexible tip 2120 comprising an inflatable balloon 2160, as shownschematically in FIGS. 5 and 6.

TABLE 1 French Diameter Diameter (Gauge) (mm) (inches) 2 0.667 0.027 31.000 0.039 4 1.333 0.053 5 1.667 0.066 6 2.000 0.079 7 2.333 0.092 82.667 0.105

By way of example, the catheter tubing may typically be about 110 cm inlength from the distal tip 2120 to the proximal end, which comprises aconnection hub 2006. This length is suitable for introduction of thecatheter into the right heart and PA through the superior vena cava(e.g. reached through the subclavian vein or interior jugular vein inthe neck, or through the median cubital vein in the arm) or the inferiorvena cava (e.g. reached through a femoral vein). For some applications,the catheter length may be shorter, e.g. 60 cm, or longer than 110 cm.

The PA catheter 2001 differs from a conventional PA catheter, in that,internally, as illustrated schematically in the longitudinalcross-sectional view in FIG. 6, it also contains a multi-sensorarrangement comprising a plurality of optical pressure sensors 10 and anoptical temperature sensor 20, and respective optical fibers 2011. Theoptical sensors 10 and 20 are not externally visible in FIG. 5, so thesensor positions are indicated schematically by P1, P2, P3 for theoptical pressure sensors and T for the optical temperature sensor. Thesensor positions P1, P2, P3 and T are located along a length L distalend portion 2130, near the distal tip 2120. As illustrated schematicallyin FIG. 5, the connection hub 2006 provides connection ports 2010-n,where n=1 . . . 7, for each of the seven lumens. Four of the connectionports, 2010-2, 2010-3, 2010-4, 2010-5 are optical connectors which arecoupled via flexible optical connections 2008 through the hub 2006 tothe optical fibers and sensors within their respective lumens, i.e.lumens 2004-2, 2004-3, 2004-4, 2004-5 shown in the transverse crosssection in FIG. 7. The optical connectors each for the four opticalsensors (P1, P2, P3 and T) plug into corresponding optical ports 2153 ofthe optical controller 2151 shown in FIG. 5.

Referring to the schematic longitudinal cross-sectional view shown inFIG. 6, and the transverse cross-sectional view shown in FIG. 7, forsimplification of illustration, the internal walls of the lumens 2004-1to 2004-7 are omitted from FIG. 6 and only the optical fibers 2011 andsensors 10 and 20 are shown within the catheter tubing; elements shownin FIG. 6 are not drawn to scale. Thus, in description of FIG. 6,references to the lumens 2004-1 to 2004-7 are made based on FIG. 7.Also, by way of example, FIG. 7 shows typical dimensions for cathetertubing comprising seven lumens and having an outside diameter of 6French (0.079 inch/2.00 mm), and for optical fibers 2011 having adiameter of 0.155 mm.

As is conventional, the PA catheter 2001 has an inflatable balloon 2160connected to a balloon inflation lumen 2004-1 which is coupled throughthe hub 2006 and flexible tubing 2007, to a balloon inflation/deflationport 2010-1. Another lumen 2004-6 provides for fluid injection orinfusion through a fluid injection/infusion port 2010-6 for injection offluid through an aperture 2012-6 located close to the sensor locationP3. A central lumen 2004-7, which has an opening 2012-7 at the distaltip 2120, has an internal diameter which is sized to receive a standardguidewire, such as a 0.025 inch guidewire, to allow forover-the-guidewire directed insertion of the PA catheter. Thus, of theseven ports 2010-n (n=1 to 7), four of those ports 2010-2, 2010-3,2010-4, 2010-5 comprise standard optical fiber connectors and the otherthree ports 2010-1, 2010-6 and 2010-7 are standard ports, such as luerfittings, i.e. for attachment of an air filled syringe for ballooninflation/deflation, for fluid injection or for guidewire insertion.

The positioning of the optical sensors 10, 20 within the catheter tubing2002 is illustrated in more detail in the schematic longitudinalcross-sectional view shown in FIG. 6. There are three optical sensors10, at sensor locations P1, P2 and P3, for measuring pressure and oneoptical sensor 20, at sensor location T, for measuring temperature. Eachoptical sensor 10 and 20 is optically coupled to a respective individualoptical fiber 2011. That is, each optical sensor is integral with asensor end of the fiber, or is bonded to the optical fiber, to providean optical coupling of the sensor and fiber. Each optical fiber,carrying its sensor at the end, extends through its own individual lumen2004-2, 2004-3, 2004-4, 2004-5 of the multi-lumen catheter, asillustrated in the transverse cross-sectional view in FIGS. 7 and 8,which are taken through plane A-A and B-B, respectively, of FIG. 6. Thecentral lumen 2004-7 is sized to accept a guidewire, such as a standard0.025 inch guidewire to facilitate insertion of the catheter. The othersix lumens are arranged symmetrically around the central lumen. A firstlumen 2004-1 and its port 2010-1 provides for balloon inflation, as isconventional, with a distal opening (2012-1 not visible) coupled to theballoon. The proximal port 2010-1 is coupled via the hub 2006 to lumen2004-1 via a length of flexible tubing 2007, and the port 2010-1 istypically a luer type fitting for connection to an air filled syringe(2100 in FIG. 5) for inflation and deflation of the balloon 2160.Second, third and fourth lumens, i.e. lumens 2004-2, 2004-3, 2004-4,each accommodate one of the optical pressure sensors 10 and its opticalfiber 2011. Each of these lumens have a respective distal aperture2012-2, 2012-3, 2012-4, adjacent to the respective sensor locations P1,P2, P3 for fluid contact. A fifth lumen 2004-5 accommodates the opticaltemperature sensor 20 and its optical fiber 2011. At the proximal end,the optical fibers 2011 for each sensor extend through a length offlexible tubing 2008 from the hub 2006 to the respective opticalconnector 2010-2, 2010-3, 2010-4, 2010-5. Thus the fibers are protectedwithin the flexible tubing 2008 to provide a flexible optical connectionof a desired length for connection to the control system. The sixthlumen, 2004-6 is provided for fluid injection of a bolus of cold fluid,to allow for flow to be determined by thermo-dilution by detection oftemperature changes by optical temperature sensor 20. This fluidinjection lumen 2004-6 has a distal opening 2012-6 positioned fordelivering fluid to the right atrium, i.e. approximately 30 cm from thedistal tip 2120, close to the sensor position P3. When the sixth lumenis not being used for injectate for thermo-dilution measurements, it mayalternatively be used for fluid infusion or injection for otherpurposes. As mentioned above, the central or seventh lumen 2004-7 isprovided for a guidewire, if guidewire assisted insertion is required.After withdrawal of the guidewire, optionally this lumen may be used forother purposes, such as blood sampling at the tip of the PA catheter,e.g. for mixed venous oxygen saturation (SvO₂) measurements, or formeasurement of cardiac output by the method of Fick.

As illustrated schematically in FIG. 6, the three optical pressuresensors 10 at sensor positions P1, P2, P3, and the optical temperaturesensor 20 at position T, are provided along a length of the distal endportion 2130 spaced by distances L₁, L₂ and L₃ from sensor position P1.P1 is located at or close to the distal tip 2120, distal to the balloon2160. P2 and P3 are arranged spaced apart lengthwise so that, in use,they can be located, respectively in the RV and the RA, when P1 ispositioned in the PA. In use, corresponding apertures 2012-2, 2012-3,2012-4 near each optical pressure sensor 10 allow for fluid contact withthe optical pressure sensors. By way of example, P2 is located at adistance L₂ from P1, typically L₂ is about 20 cm; and P3 is located at adistance L₃ from P1, typically L₃ is about 30 cm. That is, the distancebetween P1 and P2, is about 20 cm and the distance between P2 and P3, isabout 10 cm. The location of the optical temperature sensor T isproximal to the balloon and at a distance L₁ from P1, where L₁ isapproximately 4 cm, so that the temperature sensor T is located in thePA when the pressure sensors locations P1, P2 and P3 are positioned,respectively, in the PA, the RV and the RA.

The transverse cross-sectional view shown in FIG. 7 through plane A-A ofFIG. 6, illustrates the arrangement of the seven lumens of the cathetertubing of the catheter 2001 of this embodiment. There is a central lumen2004-7 for a guidewire, e.g. of a suitable diameter to receive astandard 0.025 inch guidewire. As mentioned above, the central lumen mayalso be used for fluid injection or infusion, or for blood sampling. Theother six lumens 2004-1 to 2004-6 are arranged symmetrically around thecentral guidewire lumen 2004-7. As mentioned above, three of the lumensaccommodate the three pressure sensors 10 at locations P1, P2 and P3 andtheir optical fibers 2011. One of the lumens accommodates thetemperature sensor 20 at location T and its optical fiber 2011. Onelumen, for example 2004-1, is provided for balloon inflation. The otherlumen, for example 2004-6, is provided for fluid injection or infusion.Thus, as shown schematically in the cross-sectional view in FIG. 8,through B-B of FIG. 6, an aperture or orifice 2012-4 is providedadjacent sensor P3 for fluid contact. Correspondingly, as shown inlongitudinal cross-sectional view in FIG. 6, an aperture is alsoprovided near each of the other pressure sensors 10 for fluid contactThe lumen for fluid injection has an opening 2012-6 that is locatedproximal to the aperture 2012-4 for P3 by a short distance, e.g. by 1cm, or a distance L₄, of about 31 cm from P1 at the distal tip 2120. Thespacings of the three pressure sensors 10 are selected to allow sensorlocations P2 to be placed in the RV and sensor location P3 to be placedin the RA when sensor P1 is in the PA, and so that the temperaturesensor location T is positioned in the PA for measurement of blood flowin the PA by thermo-dilution.

Referring back to FIG. 5, the proximal part of the apparatus 2001provides for optical coupling of the proximal end 2102 to the controlunit 2151. Four of the proximal ports 2010-2, 2010-3, 2010-4 and 2010-5,for the four optical sensors (P1, P2, P3 and T), comprise a standardtype of optical fiber connector, each of which connects to acorresponding optical input/output connector 2153 of the control unit2151. The control unit 2151 houses a control system comprising acontroller with appropriate functionality, e.g. including a processor,data storage, and optical source and optical detector, and it provides auser interface, e.g. a keypad 2154, and touch screen display 2152,suitable for tactile user input, and for graphical display of sensordata. The user interface connection 2155 (e.g. a standard USB cable, oralternatively, a wireless connection) is used to transfer data betweenthe control unit 2151 to the touch screen display 2152. The control unit2151 and touch screen display 2152 may optionally be integrated within asingle housing or module. As illustrated schematically in FIG. 5, eachof the optical sensors is connected by an individual optical connectorto the control unit. Alternatively, in other embodiments, the proximalends of the optical fibers for each of the optical sensors may bebundled together and coupled into a single multi-fiber proximal opticalconnector for connection to a multi-fiber optical port of the controlunit. At the proximal end 2102 of apparatus 2001, a hub 2006 coupleseach lumen of the catheter via a respective length of flexible tubing toan individual proximal port. The other three ports, 2010-1, 2010-6 and2010-7 comprise standard connections, such as Luer fittings, forattachment of a syringe or tubing. When not in use, the latter portswould typically be supplied with sterile plugs. In use, port 2010-1 isconnected to a small air filled syringe 2100 for inflation/deflation ofthe balloon tip 2160. Port 2010-6 is used for fluid injection orinfusion. Port 2010-7 is sized to accept a guidewire 2200, e.g. astandard 0.025 inch guidewire, or this port can be used for bloodsampling at the tip of the catheter.

The optical pressure sensors 10 (P1, P2, P3) are preferably Fabry-Pérot(FP) Micro-Opto-Mechanical System (MOMS) sensors, such as described byFISO Technologies (E. Pinet, “Pressure measurement with fiber-opticsensors: Commercial technologies and applications” 21st InternationalConference on Optical Fiber Sensors, edited by Wojtek J. Bock, JacquesAlbert, Xiaoyi Bao, Proc. of SPIE Vol. 7753, (2011)). These opticalpressure sensors comprise an optical fiber having a FP MOMS sensor atthe sensor end of the fiber for sensing pressure. By way of example, forstandard diameter optical fibers, each fiber (e.g., fibers 2011 in FIGS.7 and 8) has a diameter of 0.155 mm (0.006 inch) and each opticalpressure sensor (e.g., sensors 10 in FIG. 8) has a diameter of 0.260 mm(0.010 inch).

For measurement of flow by thermo-dilution, the optical temperaturesensor 20 (T) may, for example, be a GaAs (Gallium Arsenide) fiber optictemperature sensor, as described by FISO technologies (E. Pinet et al.,“Temperature fiber-optic point sensors: Commercial technologies andindustrial applications”, MIDEM Conference Proceedings, September29-Oct. 1, 2010, Radenci, Slovenia).

A typical material for fabrication of the multi-lumen catheter is aflexible polymer, such as, 4033 Pebax® (a Polyether block amide or PEBA,or other suitable thermoplastic elastomer (TPE)), which has regulatoryapproval for fabrication of conventional PA catheters. The wallthickness of the tubing may be ˜0.005 inch. The guidewire lumen has adiameter, for example, of 0.029 inch to accommodate a standard 0.025inch guidewire. Conventional coloring of the standard ports may beprovided. A different color coding may be provided for the optical portsto facilitate quick recognition and connection to correspondingly colorcoded ports of the optical controller. As illustrated schematically thetransverse cross-sectional views in FIGS. 7 and 8, sensors and fibers ofthese dimensions can be accommodated within catheter tubing 2002 havingan outside diameter of 6 French (0.079 inch or 2.0 mm—see Table 1).

For some applications a larger diameter catheter, e.g. 7 French, may beacceptable.

For smaller fibers, e.g. 0.100 mm fibers, and smaller diameter sensors,if a guidewire lumen is not required, or if the guidewire to be used issmaller than 0.025 inch, e.g. 0.018 inch, the dimensions of the lumensand the outside diameter of the catheter tubing may be reduced in sizeaccordingly, e.g. to 5 French or less.

It is preferable that the arrangement of the lumens has rotationalsymmetry about the longitudinal axis, and the wall thickness of eachlumen is selected to provide the required mechanical characteristics,such as an appropriate degree of flexibility and stiffness, withsymmetric torque characteristics along its length. For over theguidewire insertion, a more flexible catheter may be selected. Forinsertion without a guidewire, a stiffer catheter may be desirable. Forexample, while the catheter requires sufficient flexibility to traversefrom the RA into the RV and then be guided into the PA, it is alsodesirable that the catheter has sufficient stiffness or rigidity (i.e.is not too floppy) to withstand turbulent blood flow within theventricles, to withstand distortion or kinking, and to maintain aminimum bend radius of the optical fibers.

When the optical pressure sensors are FP MOMs sensors, they measurepressure at point locations of the sensor at the end of the fiber, i.e.pressure exerted on the FP membrane, and optical measurements are basedon interference measurements, i.e. frequency shifts, rather thanamplitude measurements. Blood pressure measurements are made withgreater accuracy and reliability compared to conventional pressuresensing with a fluid filled catheter and an external pressuretransducer. FP MOMS sensors can provide significantly more accuratepressure measurements, with minimal drift, compared to electricalpressure sensors, such as piezo-electric sensors. Optical pressuresensors avoid the need for multiple long thin electrical connections,which not only have significant electrical drift, but are subject tocross-talk and electro-magnetic interference. For similar reasons, it isalso preferable that for measurement of flow by thermo-dilution orthermo-convection, the temperature sensor is preferably also an opticalsensor rather than an electrical sensor. For example, forthermo-dilution measurements, the temperature sensor may be a fiberoptic sensor which measures temperature based on the temperaturedependence of a GaAs sensor at the tip of the fiber, i.e. a temperaturedependent shift in the peak wavelength of light reflected from thesensor.

FIG. 9 provides a schematic diagram of the heart 500 to illustrateplacement of the multi-sensor catheter 2001 of the first embodimentduring a right heart and PA catheterization procedure to measurepressure concurrently in the right atrium 521, right ventricle 523 andPA 525. In this example, the multi-sensor catheter 2001 is introducedinto the heart through the inferior vena cava 520, through the rightatrium 521, through the tricuspid valve 522 into the right ventricle523, through the pulmonic valve 524 and into the PA 525. The tip 2120 ofthe catheter extends into the left branch 526L of the PA. The aperture2012-2 for pressure sensor P1, which is distal to the balloon 2160 islocated in the left branch of the PA 526L. The temperature sensor T isalso in the left branch of the PA 526L, proximal to the balloon.Aperture 2012-3 for pressure sensor P2 is located in the right ventricle523. Aperture 2012-4 for pressure sensor P3 is located in the rightatrium 521. The proximal fluid injection port 2012-6 is also located inthe right atrium 521. Thus, when the optical connectors for the threeoptical pressure sensors P1, P2 and P3, and the optical temperaturesensor T are connected to the optical control system, the pressuremeasurements in the RA, RV and PA can be made concurrently. Also, theoptical temperature sensor T can be used for measurement of flow by aconventional thermo-dilution technique.

For some applications, a temperature sensor for measurement of flow bythermo-dilution may not be required, and it may be omitted.

A multi-sensor PA catheter 3001 of a second embodiment is illustrated inFIGS. 10, 11 and 12. As shown in a longitudinal cross-sectional view ofFIG. 10, in this embodiment, the multi-sensor catheter comprises threeoptical pressure sensors 10, at sensor locations similar to those of themulti-sensor PA catheter 2001 of the first embodiment, but there is notemperature sensor. As illustrated in the transverse cross-sectionalviews in FIGS. 11 and 12, in this simplified version of the multi-sensorPA catheter, the catheter tubing 3002 comprises five lumens, i.e. afirst lumen 3004-1 for balloon inflation; three lumens 3004-2, 3004-3,3004-4, one for each of the three pressure sensors 10 and its respectiveoptical fiber 3011; and the central lumen 3004-7 is provided for aguidewire, and/or for blood sampling, as described for the multi-sensorPA catheter of the first embodiment. As shown in FIG. 10, the opticalfibers 3011 for the optical pressure sensors 10 are connected from therespective lumens, through connection hub 3006, and via flexible tubing3008 to respective ports 3010-2, 3010-3 and 3010-4. Ports 3010-2,3010-3, 3010-4 comprise optical connectors for the three opticalpressure sensors 10 in the second, third and fourth lumens. Each of thethree lumens 3004-2, 3004-3, 3004-4 has a respective aperture 3012-2,3012-3 and 3012-4 for fluid contact with the respective optical pressuresensors 10. Port 3010-1 connects via tubing 3007 to the hub 3006 and thefirst lumen for inflation/deflation of the balloon 3160. Port 3010-7connects via tubing 3007 to the central lumen which has an opening3012-7 at the distal tip 3120 for a guidewire, or for blood sampling atthe tip of the catheter. Radiopaque markers 3014 are provided along thelength of the catheter tubing to assist in positioning the sensors 10within the heart. As illustrated, by way of example, in FIGS. 11 and 12,the catheter tubing has an external diameter of 6 French, and provides acentral lumen 3004-7 having an inside diameter which can accept aguidewire, e.g. a standard 0.025 inch guidewire, and four lumensarranged symmetrically around the central lumen. That is, one lumen forballoon inflation, and three lumens for three optical fibers of 0.155 mmdiameter and FP-MOMS optical pressure sensors of 0.260 mm diameter. Theoutside diameter of the PA catheter tubing may be reduced if smallerdiameter optical fibers and sensors are used, or for use with a smallerdiameter guidewire.

In comparing the multi-sensor catheters of the first and secondembodiments, comprising 7 lumens and 5 lumens respectively, it will beappreciated that the dimensions of each catheters, such as the externaldiameter, the number of lumens and the thicknesses of the internal wallsof the catheter defining each lumen are described by way of exampleonly. As mentioned above, smaller optical sensors and smaller opticalfibers may be accommodated within smaller lumens, to provide a catheterhaving a smaller outside diameter. This may be desirable for someapplications. The material from which the catheter is made, and the wallthicknesses defining the lumens, may be selected to provide the catheterwith a required stiffness or flexibility, and size.

In other alternative embodiments, when the catheter is to be flowdirected by the balloon tip, and introduction over a guidewire is notrequired, the guidewire lumen may be omitted.

For some applications, for example for pediatric or neonatal use, asignificantly smaller diameter catheter may be required, e.g. 3 French.Correspondingly, the spacings of the optical pressure sensors would becloser together, i.e. matched to the smaller dimensions of the chambersof patient's heart, for placement of one sensor in the RA, one in the RVand one in the PA. In such a case the guidewire lumen may be omitted sothat three pressure sensors can be accommodated within a multi-lumencatheter of the required diameter. While three pressure sensors aredesirable for concurrent measurements of RA, RV and PA pressurewaveforms, when a guidewire lumen is required for a smaller diametercatheter, it may only be possible to accommodate two optical pressuresensors. In this arrangement, the two sensors would be spaced apart sothat initially, one sensor can be positioned in the RA and one in the RVfor concurrent measurement of RA and RV pressure waveforms, and thensubsequently the catheter would be advanced to position one sensor inthe RV and one in the PA for concurrent measurement of RV and PApressure waveforms, and for RV and PCWP pressure waveforms.

The lengthwise spacings (L₂ and L₃) of the optical pressure sensors atlocations P1, P2 and P3 described with respect to the multi-sensorcatheters of the first and second embodiments, i.e. for measurement ofpressure waveforms concurrently in the RA, RV and PA refer to typicalspacings required for an adult human heart, where the distance from theRA to the RV is about 10 cm and the distance from the RV to the PA, in aregion downstream of the pulmonic valve, is about 10 cm. The PCWPposition is typically a further 10 cm into one of the right or leftbranches of the pulmonary artery, i.e. about 20 cm from the RV. Thus, toposition P1 in the PA near the wedge position, P2 in the RV, and P3 inthe RA, L₂ is about 20 cm and L₃ is about 30 cm. The location of thetemperature sensor T is typically positioned between P1 and P2, spaced adistance L₁ from P1, for measurement of blood flow within the PA, whereL₁ is e.g. about 4 cm to 10 cm. For pediatric and neonatal use, i.e. forsmaller sized hearts, the spacings of the sensors would be reducedaccordingly.

While it is envisaged that multi-sensor catheters for right heart and PAcatheterization may comprise more than three optical pressure sensors,there is a practical limit to how many sensors can be accommodatedwithin a multi-lumen catheter of a particular outside diameter.

Since multi-sensor PA catheters are intended as disposable, single usecatheters, in practice, the number of optical sensors may also belimited by component costs and fabrication costs. Currently, standarddiameter optical fibers and optical pressure sensors are lower cost thansmaller diameter optical fibers and optical pressure sensors. Since eachpressure sensor is in an individual lumen of the multi-lumen catheter,the available space for each lumen is also limited by the wall thicknessand tolerances for each lumen of a multi-lumen catheter. As describedherein, it is currently feasible to manufacture a multi-sensor PAcatheter with three optical pressure sensors and one optical temperaturesensor, within a 6 French multi-lumen catheter. Use of smaller fibersand sensors or smaller guidewire may allow the diameter to be reduced to5 French or less.

In a multi-sensor catheter of yet another embodiment, instead of threeoptical pressures sensors and one optical temperature sensor, it may bedesirable to have four optical pressure sensors to enable concurrentpressure measurements in the right atrium, in the right ventricle, inthe PA near the pulmonic valve and also in a branch of PA formeasurement of the PCWP.

For example, if a temperature sensor is not required for blood flowmeasurements, for example where blood flow is measured by an alternativetechnique, e.g. by the Fick method, a fourth optical pressure sensor maybe provided instead of the optical temperature sensor, so that themulti-sensor catheter can be introduced so as to position one sensor inthe RA, one sensor in the RV, one sensor in the PA, and one sensor formeasuring PCWP when the balloon is inflated. By way of example, in suchan arrangement, four pressure sensors P1, P2, P3 and P4 are spaced atintervals of ˜10 cm, i.e. the distance P1 to P2 (L₁) is 10 cm, P1 to P3(L₂) is 20 cm, and P1 to P4 (L₃) is 30 cm.

This arrangement may be desirable for longer term monitoring of pressurewaveforms in the RA, RV, PA, as well PCWP pressure waveforms. That isthe catheter may be positioned in a fixed and stable location, to enableobservation of pressure waveforms at each sensor location over anextended time period, e.g. for ICU patients requiring monitoring overseveral days or more.

Alternatively, where it is not feasible to accommodate an opticaltemperature sensor as well as the desired number of optical pressuresensors, or for cost reasons, a conventional small sized, low cost,electrical flow sensor, i.e. a thermistor, may be used, withconventional electrical connections to the control system.

In the embodiments described above, radiopaque markers may be providednear the balloon, and optionally near each sensor, to assist in locatingthe tip and positioning the sensors in use, i.e. using conventionalradio-imaging techniques, when introducing the guidewire and positioningthe pressure sensors in the right atrium, right ventricle and PA. Theradiopaque markers typically comprise a suitable heavy metal e.g.barium, tantalum, gold or platinum. Alternatively, markers are providedat regular intervals, e.g. at 10 cm intervals along the length of thecatheter tubing as is conventional for PA catheters.

Preferably that the optical fibers have some freedom to move or slidewithin the lumen when the catheter is flexed. The fibers are of theappropriate length so that the sensors at the sensor end (distal end) ofthe fibers are appropriately positioned at sensor locations in thedistal end portion of the catheter. Each of fibers may be secured nearthe proximal end, e.g. by adhesive bonding where they pass through thehub. Each fiber may also be secured in its lumen, near the sensorlocation, e.g. by injection of a medical grade adhesive through the wallof the lumen.

If required, in use, the lumens containing the fibers and sensors may beflushed with fluid, e.g. saline solution, to remove air from thecatheter lumens. Alternatively, an adhesive, or a medical grade gel, mayserve to plug the lumen each side of the aperture surrounding theoptical sensor, while leaving the sensor exposed for fluid contact. Forexample, a bolus of medical grade adhesive may be injected through thetubing to secure the fiber near each sensor and to plug the lumen aroundthe fiber. Similarly, the adhesive may also be injected into the lumendistal to the aperture. Also, if required, components of themulti-sensor catheter may be coated to reduce blood clotting, forexample, if the multi-sensor catheter is to be left in place for anextended period.

The optical pressure sensors 10 at locations P1, P2, P3 are preferablyFabry-Perot Micro-Opto-Mechanical-Systems (FP MOMS) pressure sensors. Asan example, a suitable commercially available FP MOMS pressure sensor isthe Fiso FOP-M260. These FP MOMS sensors meet specifications for anappropriate pressure range and sensitivity for blood pressuremeasurements. They have an outside diameter of 0.260 mm (260 μm).Typically, they would be attached and optically coupled (i.e. integralwith or bonded to) to a sensor end of an optical fiber with an outsidediameter of 0.100 mm (100 μm) to 0.155 mm (155 μm). Optical fibers andFP MOMS sensors of smaller diameter tend to be more expensive, and maybe used, when appropriate.

The optional optical flow sensor 20 may comprise an opticalthermo-dilution or an optical thermo-convection flow sensor, e.g. asdescribed in U.S. patent application Ser. No. 14/354,588.

For operation of the optical sensors, the optical output ports 2010-2,2010-3, 2010-4, 2012-5 couple to the respective optical ports of thecontrol unit 2151 (e.g. see FIG. 5) for controlling operation of theoptical sensors 10 and 20. The flexible tubing 2008 surrounding each ofthe optical fibers extends between the hub 2006 and the opticalconnector of the control unit to provide a flexible optical couplingfrom the hub 2006 to the control unit 2151. This tubing is provided toprotect the optical fibers and can have any appropriate diameter andflexibility. Since the catheter is intended for single use only,preferably the optical connectors are standard low cost opticalconnectors. Similarly, the flexible tubing, and other connectors for theother ports are preferably standard materials and components, such asluer fittings or other medical standard fluid ports and electricalconnectors, as appropriate, which can be sterilized, and so that themulti-sensor catheters can be provided in single-use sterile packaging,using conventional standard processes for medical devices.

For protection of the sensors during assembly, it may be preferred toinsert optical fibers and optical sensors through the respective lumenfrom the distal end of the catheter and subsequently form the opticalconnector at the proximal end, and then close the lumen at the distaltip. On the other hand, when the optical connector is pre-formed at theproximal end of the sub-assembly before insertion, the sensor end of thesub-assembly is inserted into the catheter from proximal end of therespective lumen. In either case, it is preferable that the catheterlumens have smooth rounded surfaces, with non-stick internal surfaces,i.e. to avoid sharp edges, so that the sensors and optical fibers canslide smoothly into their catheter lumen without catching on sharp edgesor corners, to avoid mechanical damage to the sensors or optical fibers.However, in use of the multi-sensor catheter, it is preferable that thefibers are fixed at the proximal end only of the catheter tubing so thatthe fibers have some freedom to move or slide within the lumens when thecatheter is flexed. If required, the optical fibers may also beadhesively bonded near the aperture to secure the sensor at theappropriate sensor location.

As mentioned above, it is desirable that the multi-sensor PA catheterhas mechanical characteristics, such as stiffness and flexibility,similar to a standard PA catheter. The optical fibers and opticalsensors do not add significant stiffness to the catheter, and thus thesecharacteristics are primarily determined by the type of material andwall thickness used for the multi-lumen catheter tubing.

Other factors for consideration are: regulatory requirements for medicaldevices, ease of use and safety. For these reasons, it is desirable thatthe materials for fabrication of a multi-sensor PA catheter are based ona conventional tried and tested PA catheter or other medical device,i.e. based on a predicate device structure which has regulatory approvaland which is fabricated with materials and components which already haveFDA and/or CE mark regulatory approval.

It will be appreciated that in alternative embodiments or variants ofthe multi-sensor catheters of the embodiments described in detail above,different combinations of one or more features disclosed herein, andfeatures disclosed in the related patent applications referenced herein,may provide multi-sensor catheters of further alternative embodiments

As disclosed herein, the cardiologist is offered multi-sensor catheterswhich have particular application for right heart and PAcatheterization. These multi-sensor catheters are configured formonitoring and diagnostic measurements of hemodynamic parameters,including concurrent measurement of blood pressure within the RA, RV andPA.

Control System and Graphical Display of Pressure Waveforms andAssociated Hemodynamic Parameters.

Referring to the control system, which was described above withreference to FIG. 5, and as described in the above referenced relatedpatent applications, it will be apparent that the control system may beused with multi-sensor catheters and multi-sensor guidewires forconcurrent blood pressure measurements at each pressure sensor location,using, two, three or more optical pressure sensors. Optionally, for flowmeasurements, the multi-sensor catheter or guidewire is further equippedwith an optical or electrical flow sensor. The control system comprisesa light source and detector and an optical interface for coupling, viarespective input/output ports, to each of the optical fibers and opticalsensors of the multi-sensor catheter or guidewire. The control systemalso comprises data storage and processing means configured forprocessing optical data indicative of pressure values and optionally,optical or electrical data indicative of flow velocity values. For usewith multi-sensor catheters and multi-sensor guidewires, for example,the multi-sensor catheter disclosed herein having three optical pressuresensors, and an optional optical flow sensor, the control system wouldhave a corresponding number of signal processing channels with opticalinputs for each of the optical sensors. The signal processing elementsfor each channel may be referred to as a signal conditioning unit. Formeasuring blood pressure and flow within the heart and blood vessels, inparticular for measuring intravascular or transvalvular blood pressuregradients, the processing means is further configured for graphicallydisplaying pressure data, and optionally flow velocity data, comprisinga plurality of blood pressure waveforms, i.e. a pressure waveform fromeach optical pressure sensor. The concurrent blood pressure waveformsfor each of the optical sensors may be displayed for one or more timeintervals, and during one or more cardiac cycles. Preferably, theprocessing means is further configured to derive hemodynamic parametersfrom the blood pressure data, and optionally from flow velocity data,and display numeric values of the parameters as well as display thepressure waveforms from each sensor. By way of example only, someschematic representations of pressure waveforms and associated numericdata, for a patient with a healthy or normally functioning heart, areshown in FIGS. 13A, 13B and 14. In practice, pressure waveforms andpressure values vary from patient to patient and may be dependent on anumber of factors, such as, whether or not the patient has a healthy ordiseased heart, or other conditions that may affect functioning of theheart. Skilled medical practitioners will recognize characteristicvariations in each pressure waveform and associated pressure values,indicative of e.g. valvular stenosis or other patient physiology.Advantageously, in use of a multi-sensor catheter, concurrent pressuremeasurements from multiple optical pressure sensors enable thecardiologist to directly compare multiple pressure waveforms, inreal-time, from the RA, RV and PA/PCWP.

As an example, FIG. 13A represents a graphical display 2152-1 showingthree blood pressure waveforms from a three sensor PA catheter: A.pressure sensor location P1 in the pulmonary artery; B. pressure sensorlocation P2 in the right ventricle; and C. pressure sensor location P3in the right atrium. Pressure units are displayed in mmHg. Optionally,it may be desirable to select and display one or multiple pressurewaveforms and related parameters in different formats. For example,during right heart and pulmonary artery catheterization with amulti-sensor catheter as disclosed herein, in addition to displayingconcurrent blood pressure waveforms from each the right atrium, rightventricle and pulmonary artery, a plurality of numeric values, such as,peak pressures, mean pressures, peak-to-peak (PK-PK) pressuredifferentials for each curve, and pressure differentials or gradientsbetween the right atrium and right ventricle, and between the rightventricle and pulmonary artery may be displayed in real time. Forexample, as illustrated schematically by the numeric data to the rightof the graphical display shown in FIG. 13A, numeric data selected fordisplay may include the mean pressure of the RA, systolic/diastolicpressure for RV/PA, a peak-to-peak gradient (PPG) for RV to PA, a PPGfor RA to RV, and heart rate HR. As is conventional, the user interfacemay include a number of buttons or keys, such as shown at the bottom ofthe display in FIG. 13A, e.g. to select parameters for display, changedisplay modes, and input identification. FIG. 13B represents a graphicaldisplay 2152-2 for three pressure waveforms, similar to that shown inFIG. 13A, except that waveform A for the PA pressure is replaced withwaveform D for the pressure sensor location P1 is in the pulmonarycapillary wedge position with the balloon inflated.

Correspondingly, in use of a multi-sensor guidewire during TAVR, e.g. amulti-sensor guidewire with two optical pressure sensors to assessfunctioning of the aortic valve, before and after a TAVR procedure. Asillustrated schematically in FIG. 14, the system comprises a graphicaldisplay 2052-3 which shows two pressure waveforms: A. from pressuresensor location P1 in the left ventricle and B. from pressure sensorlocation P2 in the aorta, together with numeric values derived from thepressure waveforms from the left ventricle and aorta, e.g. atransvalvular pressure gradient. For example, the system mayautomatically compute an aortic regurgitation index (ARi or AR Index)and display the ARi value in real time. The ARi may be computed frommeasured values of the left ventricular end-diastolic pressure (LVEDP),diastolic blood pressure (DBP), and systolic blood pressure (SBP), asillustrated in FIG. 14. and is defined as:ARi=((DBP−LVEDP)/SBP)×100

In one embodiment, the control system comprises a signal processing unitfor receiving optical data and optionally electrical data, from amulti-sensor catheter or guidewire. The signal processing unit iscoupled by a data connection to a general purpose computer system, whichmay be personal computer (PC), such as a laptop or tablet PC, comprisingprocessing means, i.e. one or more processors and a computer programproduct, embodied in a non-transitory computer readable medium storinginstructions, in the form of code, for execution by the processingmeans. The computer program product is, for example, a softwareapplication comprising instructions for execution in a processor of thetablet PC for receiving or retrieving data, and displaying a pluralityof concurrent pressure waveforms from the optical pressure sensors, andfor computing, and displaying in real-time, associated hemodynamicparameters or an index, such as ARi.

In another example of a TVT procedure, a multi-sensor guidewire orcatheter may be used for measurement of concurrent pressure waveformsupstream and downstream of the mitral valve, e.g. to assess functioningof the mitral valve before and after TMVI.

For example, the tablet PC is configured for graphically displayingpressure data, and optionally flow velocity data, e.g. comprising aplurality of blood pressure waveforms. The concurrent blood pressurewaveforms for each optical sensor may be displayed for one or more timeintervals, and during one or more cardiac cycles. The processing meansis further configured to derive and display hemodynamic parameters fromthe blood pressure data and flow velocity data. For example, duringright heart and pulmonary artery catheterization with a multi-sensorcatheter as disclosed herein, in addition to displaying blood pressurewaveforms from the right atrium, right ventricle and pulmonary artery, aselected plurality of numeric values such as peak pressures, meanpressures, peak to peak pressure differentials for each curve, andpressure differentials or gradients between the right atrium and rightventricle, and between the right ventricle and pulmonary artery can bedisplayed in real time.

As is conventional, the system may comprise a user interface, such as akeyboard or touchscreen, to allow the operator to select from availableinformation which waveforms or parameters are to be displayed. Theinterface may allow the operator to input user data such as patientidentification, and data interfaces may be provide to output data toother devices or systems, or receive data from other sources, such asfrom other sensors or monitoring systems, which are typically used in anICU or OR. For example, in a cardiac catheterization laboratory, thecontrol system for a multi-sensor catheter or guidewire may be coupledto, or part of, a computing system controlling other equipment, andwhich is equipped with one or more large screen displays close to theoperating table, and other remote displays in a monitoring area. Thelatter are used to display various forms of data, sequentially,concurrently, or on demand. Such data may include, e.g. fluoroscopicimaging, with or without contrast media, and transesophagealecho-cardiography (TEE) images, as well as sensor data comprisingpressure waveforms from the multi-sensor catheter or guidewire andassociated hemodynamic parameters calculated or derived from thereceived optical pressure sensor data.

While a specialized signal processing unit or interface, which may bereferred to as a “signal conditioner”, is used to receive optical datafrom the multi-sensor catheter or multi-sensor guidewire, and generateoutput data indicative of pressure for display of pressure waveforms,the output data may be fed by a standard data connection, wired orwireless, to a processor, such as a general purpose computer, which isconfigured to provide the required functionality. For example, thesystem includes a processor and a computer program product (typicallyreferred to as a software application or computer code), embodied in anon-transitory computer readable medium storing instructions, forexecution in a processor of a control system for a multi-sensor catheteror a multi-sensor guidewire, for processing optical data receivedconcurrently from a plurality of optical pressure sensors indicative ofblood pressure, displaying a corresponding plurality of blood pressurewaveforms, and optionally flow velocity data, and displaying numericdata relating to selected hemodynamic parameters and indexes.

TABLE 2 Abbreviations or acronyms ARi or AR Index Aortic RegurgitationIndex Cath Lab Cardiac Catheterization Laboratory CO Cardiac Output CVCCentral Venous Pressure catheter DBP Diastolic Blood Pressure FP MOMSSensor Fabry-Pérot Micro-Opto-Mechanical- System Sensor ICU IntensiveCare Unit LAP Left Atrial Pressure LVEDP Left Ventricular End-DiastolicPressure OR Operating Room PA Pulmonary Artery PCWP Pulmonary CapillaryWedge Position/ Pressure PEBA PolyEther Block Amide RA Right Atrium RHCRight Heart Catheterization RV Right Ventricle SvO₂ Mixed venous oxygensaturation SBP Systolic Blood Pressure TAVI or TAVR Transcatheter AorticValve Implantation or Replacement TMVI or TMVR Transcatheter MitralValve Implantation or Replacement TPE Thermoplastic elastomer TVRTranscatheter heart Valve Replacement TVT Transcatheter Valve Therapies(TVT).

INDUSTRIAL APPLICABILITY

Multi-sensor PA catheters according to embodiments of the inventiondisclosed herein provide real-time, concurrent, multi-chamber (RA andRV) pressure measurements within the right heart and also the PA. Eachpressure measurement is taken concurrently under identical and stableconditions, while the multi-sensor catheter is positioned to locate onesensor in each of the RA, RV and PA.

In contrast, during RHC using a conventional PA catheter, it isnecessary to move the catheter to get each pressure measurement, so eachmeasurement is taken at a different time, under different conditions.For example, withdrawing a PA catheter from the PA to the RV may causecardiac arrhythmia or premature ventricular contraction (PVC). That is,the instantaneous condition for each pressure measurement is impacted bymoving the catheter.

In some instances, such as monitoring in an ICU, it may be too risky tomove the PA catheter once the catheter tip is placed in the PA. For aconventional PA catheter, it would then only provide the PA pressure,not a RV and RA pressure. Thus, where appropriate, the multi-sensorcatheter offers continuous real-time and concurrent monitoring of all ofRA, RV and PA pressures for an extended time, e.g. over a period ofdays, for an ICU patient. In this scenario, RA pressure monitoringprovides alternative to monitoring of central venous pressure (CVP).

For post-operative monitoring, there may be risks in use of a Swan Ganzcatheter, and there is a need to appropriately select patients who needSwan Ganz catheterization. For patients where Swan Ganz catheterizationis appropriate, the multi-sensor PA catheter offers continuous real-timeand concurrent monitoring of all of RA, RV and PA pressures.

Since these pressure measurements also provide an indirect measure ofleft heart hemodynamic parameters, these measurements can help toidentify pathology and physiological problems and select appropriatetherapies, drugs, and procedures. For example, pressure measurements mayhelp to differentiate patient physiologies, and identify a fillingproblem vs. a valve problem, such as, an obstruction of the tricuspidvalve.

For example, multiple concurrent blood pressure measurements during RHCmay show, e.g., a high RA pressure and a low RV pressure, which mayindicate tricuspid valve stenosis/obstruction. In conditions such aspulmonary edema, concurrent pressure measurements of the RA, RV, PA andPCWP may provide information which helps to determine or differentiate,e.g., whether is symptoms are caused by a RH or LH problem, a valveproblem (stenosis or regurgitation), a muscle problem, cardiacrestriction or constriction, PA hypertension, or a primary lung problem(such as Acute Respiratory Distress Syndrome).

The number of TAVR procedures per year is projected to increasedramatically in the next few years. During left heart catheterizationfor TAVR, the Aortic Regurgitation index (ARi) is a widely usedparameter for assessing function of the aortic valve before and aftervalve repair or replacement. It is also expected that the mitral valvereplacement will increase in future years, but aortic valve replacementis much more common.

By comparison, pulmonic valve interventions are rare and there is not acommonly used PA index. However, multi-sensor catheters providingconcurrent pressure measurements in the RA, RV and PA may allow for anappropriate index to be adopted for RHC.

Although embodiments of the invention have been described andillustrated in detail, it is to be clearly understood that the same isby way of illustration and example only and not to be taken by way oflimitation, the scope of the present invention being limited only by theappended claims.

The invention claimed is:
 1. A multi-sensor catheter for right heart andpulmonary artery catheterization, comprising: a length of multi-lumencatheter tubing extending between a proximal end and a distal end,having an outside diameter of ≤8 French, and the distal end comprisingan atraumatic tip; a plurality of optical sensors and a plurality ofoptical fibers; a sensor end of each optical fiber being attached andoptically coupled to an individual one of the plurality of opticalsensors; each optical sensor and its optical fiber being inserted into arespective lumen of the multi-lumen catheter tubing, the sensors beingspaced apart lengthwise to provide a sensor arrangement with saidplurality of optical sensors positioned at respective sensor locationsspaced apart lengthwise within a distal end portion of the cathetertubing; a proximal end of each of the plurality of optical fibers beingcoupled to an optical input/output connector at the proximal end of themulti-sensor catheter for connection to an optical control system; andthe plurality of optical sensors of the sensor arrangement comprising atleast three optical pressure sensors at respective sensor locationsspaced apart lengthwise along said length of said distal end portion,with an aperture in the catheter tubing adjacent each optical pressuresensor for fluid contact; and wherein the pressure sensor locations andspacings are configured to place at least one pressure sensor in each ofthe right atrium, the right ventricle and the pulmonary artery duringright heart and pulmonary artery catheterization, for concurrent bloodpressure measurements at each optical pressure sensor location.
 2. Themulti-sensor catheter of claim 1, further comprising another lumenhaving a proximal port and an opening at the distal tip of the cathetertubing, said lumen having a diameter which accepts a guidewire.
 3. Themulti-sensor catheter of claim 1, further comprising an inflatableballoon near the distal tip, the catheter tubing further comprising aballoon inflation lumen, the inflatable balloon being coupled by theballoon inflation lumen to a balloon inflation port at the proximal endof the catheter tubing.
 4. The multi-sensor catheter of claim 1, furthercomprising: an inflatable balloon near the distal tip, the cathetertubing further comprising a balloon inflation lumen, the inflatableballoon being coupled by the balloon inflation lumen to a ballooninflation port at the proximal end of the catheter tubing; and anotherlumen having a proximal port and an opening at the distal tip of thecatheter tubing, said lumen having a diameter which accepts a guidewire.5. The multi-sensor catheter of claim 1, wherein the plurality ofoptical sensors further comprises an optical flow sensor.
 6. Themulti-sensor catheter of claim 5, wherein the flow sensor comprises anoptical thermo-dilution sensor positioned proximal to the distal tip forplacement in the pulmonary artery and the catheter tubing furthercomprises a fluid injection lumen having an aperture positioned forfluid injection into the right atrium and the fluid injection lumenbeing coupled at the proximal end of the multi-lumen catheter to a fluidinjection port.
 7. The multi-sensor catheter of claim 1, wherein: theplurality of optical sensors further comprises an opticalthermo-dilution sensor positioned proximal to the distal tip forplacement in the pulmonary artery and the catheter tubing furthercomprises a fluid injection lumen having an aperture positioned forfluid injection into the right atrium and the fluid injection lumenbeing coupled at the proximal end of the multi-lumen catheter to a fluidinjection port; and further comprising: an inflatable balloon near thedistal tip, the catheter tubing further comprising a balloon inflationlumen, the inflatable balloon being coupled by the balloon inflationlumen to a balloon inflation port at the proximal end of the cathetertubing; and another lumen having a proximal port and an opening at thedistal tip of the catheter tubing, said lumen having a diameter whichaccepts a guidewire.
 8. The multi-sensor catheter of claim 1, whereinthe multi-lumen catheter tubing has an outside diameter in the rangefrom 4 to 7 French.
 9. The multi-sensor catheter of claim 1, furthercomprising another lumen having a proximal port and an opening at thedistal tip of the catheter tubing, said lumen having a diameter whichaccepts a standard guidewire, of 0.025 inch diameter or less, and theoutside diameter of the multi-lumen tubing is 6 French or less.
 10. Themulti-sensor catheter of claim 1, further comprising radiopaque markersfor location of each of the optical sensors.
 11. The multi-sensorcatheter of claim 1, wherein the proximal end of the multi-lumencatheter comprises a hub, through which each lumen of the multi-lumencatheter is connected to an individual length of flexible tubing andrespective individual proximal ports; the proximal ports for eachoptical sensor comprising said optical input/output connector, and theoptical fibers for each optical sensor extending through from theoptical sensor through its respective individual lumen of themulti-lumen catheter tubing, through the hub and flexible tubing to therespective optical input/output connector for connection to the opticalcontrol system.
 12. The multi-sensor catheter of claim 1, wherein theoptical pressure sensors comprise Fabry-Pérot Micro-Opto-MechanicalSystem (FP MOMS) sensors having a diameter of 0.260 mm or less.
 13. Themulti-sensor catheter of claim 1, wherein the optical pressure sensorscomprise Fabry-Pérot Micro-Opto-Mechanical System (FP MOMS) sensorshaving a diameter of 0.260 mm or less and wherein the multi-sensorcatheter further comprises at least one of: a) another lumen having aproximal port and an opening at the distal tip of the catheter tubing,said lumen having a diameter which accepts a guidewire; b) an inflatableballoon near the distal tip, the catheter tubing further comprising aballoon inflation lumen, the inflatable balloon being coupled by theballoon inflation lumen to a balloon inflation port at the proximal endof the catheter tubing; c) a flow sensor comprising an opticalthermo-dilution sensor positioned proximal to the distal tip forplacement in the pulmonary artery and the catheter tubing furthercomprises a fluid injection lumen having an aperture positioned forfluid injection into the right atrium and the fluid injection lumenbeing coupled at the proximal end of the multi-lumen catheter to a fluidinjection port; d) a flow sensor comprising a thermistor positionedproximal to the distal tip for placement in the pulmonary artery and thecatheter tubing further comprises a fluid injection lumen having anaperture positioned for fluid injection into the right atrium and thefluid injection lumen being coupled at the proximal end of themulti-lumen catheter to a fluid injection port; e) radiopaque markersfor location of each of the optical sensors; f) the proximal end of themulti-lumen catheter comprises a hub, through which each lumen of themulti-lumen catheter is connected to an individual length of flexibletubing and respective individual proximal ports; the proximal ports foreach optical sensor comprising said optical input/output connector, andthe optical fibers for each optical sensor extending through from theoptical sensor through its respective individual lumen of themulti-lumen catheter tubing, through the hub and flexible tubing to therespective optical input/output connector for connection to the opticalcontrol system; g) the outside diameter of the multi-lumen tubing is 6French or less; h) adhesive or gel securing each sensor and opticalfiber near the sensor location within the respective lumen; i) a coatingto reduce blood clotting; and j) a combination of two or more offeatures a) to i).
 14. A multi-sensor catheter for right heart andpulmonary artery catheterization in pediatric or neonatal patients,comprising: a length of multi-lumen catheter tubing extending between aproximal end and a distal end, having an outside diameter of ≤3 French,and the distal end comprising an atraumatic tip; a plurality of opticalsensors and a plurality of optical fibers; a sensor end of each opticalfiber being attached and optically coupled to an individual one of theplurality of optical sensors; each optical sensor and its optical fiberbeing inserted into a respective lumen of the multi-lumen cathetertubing, the sensors being spaced apart lengthwise to provide a sensorarrangement with said plurality of optical sensors positioned atrespective sensor locations spaced apart lengthwise within a distal endportion of the catheter tubing; a proximal end of each of the pluralityof optical fibers being coupled to an optical input/output connector atthe proximal end of the multi-sensor catheter for connection to anoptical control system; and the plurality of optical sensors of thesensor arrangement comprising at least two optical pressure sensors atrespective sensor locations spaced apart lengthwise along said length ofsaid distal end portion, with an aperture in the catheter tubingadjacent each optical pressure sensor for fluid contact; and wherein thepressure sensor locations and spacings are configured to measureconcurrent pressure waveforms for at least two locations within theright heart and pulmonary artery comprising a right atrial pressurewaveform, a right ventricular waveform, a pulmonary artery waveform anda pulmonary capillary wedge position waveform, to provide concurrentblood pressure measurements at each optical pressure sensor location.15. A multi-sensor catheter for right heart and pulmonary arterycatheterization comprising: a length of multi-lumen catheter tubingextending between a proximal end and a distal end, having an outsidediameter sized to allow insertion through a vein in an upper or lowerarm, and the distal end comprising an atraumatic tip; a plurality ofoptical sensors and a plurality of optical fibers; a sensor end of eachoptical fiber being attached and optically coupled to an individual oneof the plurality of optical sensors; each optical sensor and its opticalfiber being inserted into a respective lumen of the multi-lumen cathetertubing, the sensors being spaced apart lengthwise to provide a sensorarrangement with said plurality of optical sensors positioned atrespective sensor locations spaced apart lengthwise within a distal endportion of the catheter tubing; a proximal end of each of the pluralityof optical fibers being coupled to an optical input/output connector atthe proximal end of the multi-sensor catheter for connection to anoptical control system; and the plurality of optical sensors of thesensor arrangement comprising at least two optical pressure sensors atrespective sensor locations spaced apart lengthwise along said length ofsaid distal end portion, with an aperture in the catheter tubingadjacent each optical pressure sensor for fluid contact; and wherein thepressure sensor locations and spacings are configured to measureconcurrent pressure waveforms for at least two locations within theright heart and pulmonary artery comprising a right atrial pressurewaveform, a right ventricular waveform, a pulmonary artery waveform andpulmonary capillary wedge position waveform, to provide concurrent bloodpressure measurements at each optical pressure sensor location.
 16. Themulti-sensor catheter of claim 15, wherein the optical pressure sensorscomprise Fabry-Pérot Micro-Opto-Mechanical System (FP MOMS) sensorshaving a diameter of 0.260 mm or less and wherein the multi-sensorcatheter further comprises at least one of: a) another lumen having aproximal port and an opening at the distal tip of the catheter tubing,said lumen having a diameter which accepts a guidewire; b) an inflatableballoon near the distal tip, the catheter tubing further comprising aballoon inflation lumen, the inflatable balloon being coupled by theballoon inflation lumen to a balloon inflation port at the proximal endof the catheter tubing; c) a flow sensor comprising an opticalthermo-dilution sensor positioned proximal to the distal tip forplacement in the pulmonary artery and the catheter tubing furthercomprises a fluid injection lumen having an aperture positioned forfluid injection into the right atrium and the fluid injection lumenbeing coupled at the proximal end of the multi-lumen catheter to a fluidinjection port; d) a flow sensor comprising a thermistor positionedproximal to the distal tip for placement in the pulmonary artery and thecatheter tubing further comprises a fluid injection lumen having anaperture positioned for fluid injection into the right atrium and thefluid injection lumen being coupled at the proximal end of themulti-lumen catheter to a fluid injection port; e) radiopaque markersfor location of each of the optical sensors; f) the proximal end of themulti-lumen catheter comprises a hub, through which each lumen of themulti-lumen catheter is connected to an individual length of flexibletubing and respective individual proximal ports; the proximal ports foreach optical sensor comprising said optical input/output connector, andthe optical fibers for each optical sensor extending through from theoptical sensor through its respective individual lumen of themulti-lumen catheter tubing, through the hub and flexible tubing to therespective optical input/output connector for connection to the opticalcontrol system; g) adhesive or gel securing each sensor and opticalfiber near the sensor location within the respective lumen; and h) acoating to reduce blood clotting.